Using sera and renal biopsies obtained from acute post streptococcal glomerulonephritis patients (APSGN), we have now established that all nephritogenic strains secrete a protein that binds to human plasmin. This protein has now been identified as streptococcal pyrogenic exotoxin B originally described as streptococcal proteinase. The sera of APSGN patients react preferentially with this protein and approximately 50-60% of the APSGN biopsies contain this protein. Essentially similar results were obtained by Vogt's group who called their protein cationic protein. Thus we have a potential proteinase which has the property of binding to activated plasmin (another proteinase). The combined molecule can activate the complement cascade, trigger cytokines and lymphokines and is chemotactic for neutrophils and macrophages - all hallmarks of the disease. Our current efforts will be to expand on further biological properties of this protein and to develop an experimental mouse model of nephritis using strains that are + or - for SEB production. Studies involving the Rheumatic Fever marker D8/17 have proceeded along two areas of investigation. The first is concerned with the predictive role of the marker for disease susceptibility. Approximately 3,000 children ages 5-10 years who come from high risk areas of rheumatic fever in Mexico City have been tested for the marker. Seven percent of these unaffected children are positive for the marker. All children are being followed over time for the appearance of rheumatic fever. If our hypothesis is correct, only those positive for the D8/17 marker will be susceptible. The second area of investigation of the marker was unexpected. In collaboration with a group from Child Psychiatry at NIH under the direction of Dr. Sue Swedo, we have examined the presence or absence of this marker in a group of 23 children (and appropriate controls) with obsessive-compulsive disorders (OCD). In a double blind test the marker correctly identified ninety percent of the OCD patients compared to the expected 7% controls. In view of the known cross-reactions between streptococcal antigens and caudate nucleus cells, these studies suggest that other brain- streptococcal cross reactive antigens may be involved in the OCD syndrome.